Mak W Ashwin, Wapperom Daphne, Redel Anne-Lotte, Koeleman Johannes G M, Smit Pieter W, Lam-Tse Wai-Kwan, van der Poll Tom, Chen Hung-Jen, den Dunnen Jeroen, Braunstahl Gert-Jan, Ong David S Y
Department of Medical Microbiology and Infection Control, Franciscus Hospital, Rotterdam, the Netherlands.
Center for Infection and Molecular Medicine, Amsterdam Institute for Immunology and Infectious Diseases, Amsterdam University Medical Centers, Amsterdam, the Netherlands.
J Med Virol. 2025 Sep;97(9):e70582. doi: 10.1002/jmv.70582.
Long COVID (LC) is a post-acute infection syndrome affecting 5%-10% of individuals infected by SARS-CoV-2. Here, we aimed to study SARS-CoV-2 humoral immunity, immunological imprinting by endemic coronaviruses, and previous herpesvirus infections in LC. We included 47 LC patients and 41 controls who fully recovered from COVID-19. We assessed IgG, IgA, and IgM antibody levels against SARS-CoV-2, seasonal coronaviruses, and herpesviruses using ELISAs and Microblot-Array panels. Additionally, we performed PCR to detect viral RNA/DNA and evaluated anti-nuclear autoantibodies linked to systemic autoimmune conditions. LC patients showed significantly reduced levels of SARS-CoV-2 anti-spike IgG and IgA but increased levels of endemic coronaviruses OC43 and HKU1 anti-spike IgG, suggesting immunological imprinting potentially driven by these coronaviruses. Furthermore, LC patients had higher levels of SARS-CoV-2 anti-spike IgM compared to anti-Spike IgG, possibly indicating impaired class switching. Interestingly, cytomegalovirus (CMV) p65 IgG levels were lower in LC patients and negatively correlated with fatigue severity. This study highlights immunological imprinting by seasonal coronaviruses and impaired antibody class switching as potential causes of SARS-CoV-2 immune escape and persistence in LC patients. Furthermore, our findings suggest an inverse association between CMV p65 IgG and fatigue severity in LC.
长期新冠(LC)是一种急性感染后综合征,影响5%-10%的新冠病毒感染者。在此,我们旨在研究长期新冠患者中新冠病毒的体液免疫、地方性冠状病毒的免疫印记以及既往疱疹病毒感染情况。我们纳入了47例长期新冠患者和41例从新冠中完全康复的对照者。我们使用酶联免疫吸附测定(ELISA)和微印迹阵列板评估了针对新冠病毒、季节性冠状病毒和疱疹病毒的IgG、IgA和IgM抗体水平。此外,我们进行了聚合酶链反应(PCR)以检测病毒RNA/DNA,并评估了与系统性自身免疫性疾病相关的抗核自身抗体。长期新冠患者的新冠病毒抗刺突IgG和IgA水平显著降低,但地方性冠状病毒OC43和HKU1的抗刺突IgG水平升高,这表明这些冠状病毒可能驱动了免疫印记。此外,与抗刺突IgG相比,长期新冠患者的新冠病毒抗刺突IgM水平更高,这可能表明类别转换受损。有趣的是,长期新冠患者的巨细胞病毒(CMV)p65 IgG水平较低,且与疲劳严重程度呈负相关。这项研究强调了季节性冠状病毒的免疫印记和抗体类别转换受损是长期新冠患者中新冠病毒免疫逃逸和持续存在的潜在原因。此外,我们的研究结果表明长期新冠患者中CMV p65 IgG与疲劳严重程度呈负相关。
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